Infection with the human immunodeficiency virus (HIV) commonly involves the central nervous system. The most frequent neuropsychiatric syndrome due to infection with HIV is a debilitating progressive demintia complex (ADC). The pathogenesis of ADC is not known, but appears to be due to undefined secondary viral effects rather than direct cell infection. Based on our positive preliminary data-the demonstration of specific antibrain antibody on Western blots and indirect immunofluorescence- this proposal will explore the role of autoantibodies (autoAbs) to brain components in ADC. Specimens will be examined from existing banks of samples collected from ADC patients and controls: sera (n greater than 1000), paired CSF and sera (n=100),and brain plus paired CSF and sera (n=50). Ongoing collection of specimens will continue from patients who are being evaluated by formal neuropsychological and neurologic protocols. Extensive controls will be included. CSF and serum will be examined for autoAb to whole brain, specific brain antigens (including myelin basic protein, gangliosides, n-CAM, galactocerebroside) and cell lystes (including neuronal and glial lines). Both the technique of Western immunoblots and indirect immunofluorescene will be used for the above examination. Immunohistochemistry will be used to look for in-situ brain autoAb. In addition, the immune complexes (IC) we detect in the CSF from ADC patients will be isolated and dissociated, and the IC components examined for brain reactivity as well as HIV components. IC will be measured using 3 assays (Raji cell, solid phase Clg, and PEG-ELISA) and isolated by Raji cell elution or PEG precipitation. Data will be analyzed using appropriate statistical methods. The proposal should help determine whether an autoimmune process is linked to ADC. It should also contribute more broadly to information on the potential role of viruses and autoimmune disturbances in dementing and neuropsychiatric diseases.